3-(o-nitrobenzyloxy)phenol | 76039-57-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(o-nitrobenzyloxy)phenol
• 英文别名: 3-[(2-nitrophenyl)methoxy]phenol；3-(2-nitrobenzyloxy)phenol
• CAS: 76039-57-1
• 化学式: C₁₃H₁₁NO₄
• mdl: MFCD11540375
• 分子量: 245.235
• InChiKey: KNSHAISEXHWQLE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.076
• 拓扑面积：
  75.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(o-nitrobenzyloxy)phenol 在 盐酸 、 platinum(IV) oxide 、 氯化亚砜 、 偶氮二甲酸二异丙酯 、 氢气 、 sodium cyanoborohydride 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 三苯基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 水 为溶剂， 70.0 ℃ 、101.33 kPa 条件下， 反应 4.75h， 生成 4-methyl-N-[2-[[3-[(1-methyl-4-piperidyl)oxy]phenoxy]methyl]-phenyl]thieno[3,2-b]pyrrole-5-carboxamide
  参考文献：
  名称：

  Thieno[3,2-b]pyrrole-5-carboxamides as New Reversible Inhibitors of Histone Lysine Demethylase KDM1A/LSD1. Part 2: Structure-Based Drug Design and Structure–Activity Relationship

  摘要：

  The balance of methylation levels at histone H3 lysine 4 (H3K4) is regulated by KDM1A (LSD1). KDM1A is overexpressed in several tumor types, thus representing an emerging target for the development of novel cancer therapeutics. We have previously described (Part 1, DOI 10.1021.acs.jmedchem.6b01018) the identification of thieno[3,2-b]pyrrole-5-carboxamides as novel reversible inhibitors of KDM1A, whose preliminary exploration resulted in compound 2 with biochemical IC50 = 160 nM. We now report the structure-guided optimization of this chemical series based on multiple ligand/KDM1A-CoRest cocrystal structures, which led to several extremely potent inhibitors. In particular, compounds 46, 49, and 50 showed single-digit nanomolar IC50 values for in vitro inhibition of KDM1A, with high selectivity in secondary assays. In THP-1 cells, these compounds transcriptionally affected the expression of genes regulated by KDM1A such as CD14, CD11b, and CD86. Moreover, 49 and SO showed a remarkable anticlonogenic cell growth effect on MLL-AF9 human leukemia cells.

  DOI：

  10.1021/acs.jmedchem.6b01019
• 作为产物：
  描述：

  2-硝基苄溴 、 间苯二酚 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 以48%的产率得到3-(o-nitrobenzyloxy)phenol
  参考文献：
  名称：

  Light-Activated Regulation of Cofilin Dynamics Using a Photocaged Hydrogen Peroxide Generator

  摘要：

  Hydrogen peroxide (H2O2) can exert diverse signaling and stress responses within living systems depending on its spatial and temporal dynamics. Here we report a new small-molecule probe for producing H2O2 on demand upon photoactivation and its application for optical regulation of cofilin-actin rod formation in living cells. This chemical method offers many potential opportunities for dissecting biological roles for H2O2 as well as remote control of cell behavior via H2O2-mediated pathways.

  DOI：

  10.1021/ja107783j

文献信息

• Further studies on the cyclisation of 3-hydroxy-2'-nitrodiphenyl ethers and related compounds
  作者：C.W. Bird、M. Latif

  DOI：10.1016/0040-4020(80)80079-2

  日期：1980.1

  been examined as a potential route to 1H-phenoxazinones. Unexpectedly, cyclisation of the dichloro compound proceeded with loss of a Cl and yielded 2-chloro-3H-phenoxazin-3-one. The cyclisation of a range of analogous substrates has been investigated and shown to provide novel and convenient syntheses of 3-amino-phenoxazine, 3H-phenothiazin-3-one and 8-hydroxy-5,10-dihydro-11H-dibenzo[b,e][1,4]diazepin-11-one

  已经研究了3-羟基-2′-硝基二苯基醚的4，6-二甲基和4，6-二氯衍生物的还原环化作为制备1H-苯恶嗪酮的潜在途径。出乎意料的是，二氯化合物的环化在失去Cl的情况下进行并产生了2-氯-3H-苯恶嗪-3-酮。已研究了一系列类似底物的环化作用，并证明它们可提供新颖，方便的合成方法，包括3-氨基-吩恶嗪，3H-吩噻嗪-3-酮和8-羟基-5,10-二氢-11H-二苯并[b， e] [1,4] diazepin-11-one。
• Light-Activated Regulation of Cofilin Dynamics Using a Photocaged Hydrogen Peroxide Generator
  作者：Evan W. Miller、Nicolas Taulet、Carl S. Onak、Elizabeth J. New、Julie K. Lanselle、Gillian S. Smelick、Christopher J. Chang

  DOI：10.1021/ja107783j

  日期：2010.12.8

  Hydrogen peroxide (H2O2) can exert diverse signaling and stress responses within living systems depending on its spatial and temporal dynamics. Here we report a new small-molecule probe for producing H2O2 on demand upon photoactivation and its application for optical regulation of cofilin-actin rod formation in living cells. This chemical method offers many potential opportunities for dissecting biological roles for H2O2 as well as remote control of cell behavior via H2O2-mediated pathways.
• BIRD C. W.; LATIF M., TETRAHEDRON, 1980, 36, NO 12, 1813-1816
  作者：BIRD C. W.、 LATIF M.

  DOI：——

  日期：——
• Thieno[3,2-<i>b</i>]pyrrole-5-carboxamides as New Reversible Inhibitors of Histone Lysine Demethylase KDM1A/LSD1. Part 2: Structure-Based Drug Design and Structure–Activity Relationship
  作者：Paola Vianello、Luca Sartori、Federica Amigoni、Anna Cappa、Giovanni Fagá、Raimondo Fattori、Elena Legnaghi、Giuseppe Ciossani、Andrea Mattevi、Giuseppe Meroni、Loris Moretti、Valentina Cecatiello、Sebastiano Pasqualato、Alessia Romussi、Florian Thaler、Paolo Trifiró、Manuela Villa、Oronza A. Botrugno、Paola Dessanti、Saverio Minucci、Stefania Vultaggio、Elisa Zagarrí、Mario Varasi、Ciro Mercurio

  DOI：10.1021/acs.jmedchem.6b01019

  日期：2017.3.9

  The balance of methylation levels at histone H3 lysine 4 (H3K4) is regulated by KDM1A (LSD1). KDM1A is overexpressed in several tumor types, thus representing an emerging target for the development of novel cancer therapeutics. We have previously described (Part 1, DOI 10.1021.acs.jmedchem.6b01018) the identification of thieno[3,2-b]pyrrole-5-carboxamides as novel reversible inhibitors of KDM1A, whose preliminary exploration resulted in compound 2 with biochemical IC50 = 160 nM. We now report the structure-guided optimization of this chemical series based on multiple ligand/KDM1A-CoRest cocrystal structures, which led to several extremely potent inhibitors. In particular, compounds 46, 49, and 50 showed single-digit nanomolar IC50 values for in vitro inhibition of KDM1A, with high selectivity in secondary assays. In THP-1 cells, these compounds transcriptionally affected the expression of genes regulated by KDM1A such as CD14, CD11b, and CD86. Moreover, 49 and SO showed a remarkable anticlonogenic cell growth effect on MLL-AF9 human leukemia cells.